Introduction:

Estimated prevalence of familial hypercholesterolemia (FH) in the general population is about 0.32% (roughly 1 in 313 people) from the large metaanalysis report worldwide and 1:250 individuals in general population to be 5 million in India. One of the important risks for cardiovascular disease (CVD). The demand for novel treatment strategies is growing, and gene therapy represents a promising alternative for improving FH management.

Aim & Objective:

To determine the various treatment modalities options of familial hypercholesterolemia from various studies.

Material and Methods: 

Various studies from Embase, PubMed, and the Web of Science were searched until Dec, 2024, systemic review, metaanalysis, peer-reviewed papers and conference abstracts were analysed. This review begins with an overview of approved gene therapy drugs , examines gene addition, gene inactivation, and gene editing strategies for hypercholesterolemia, emphasizing currently approved interventions as well as emerging candidates, recent progress in gene-editing technologies essential for their use in gene therapy.

Results:

Lipid lowering gene activation therapy are siRNA therapies targeting PCSK9, ANGPTL3, APOC3, and Lp(a) show promising lipid-lowering effects. Inclisiran, an siRNA against PCSK9, is approved for HeFH and ASCVD, reducing LDL-C by 44% (Ray et al.). ARO-ANG3 lowers non-HDL-C by up to 32% in HoFH and mixed dyslipidemia (Watts et al.). ARO-APOC3 achieves up to 27% non-HDL-C reduction in mixed dyslipidemia and hypertriglyceridemia (Vasas et al.). ASO therapies show similar potential; Mipomersen (apoB-100), though discontinued, lowered LDL-C by 25% in HoFH (Raal et al. Vupanorsen targeting ANGPTL3(phase2b) lowering non-HDL-C by 28% (Bergmark et al.), Volanesorsen, an APOC3 ASO (phase 3) reducing non-HDL-C by 46% in hypertriglyceridemia/FCS (Witztum et al ), Enlicitide PCSK9 inhibitor for adults with heterozygous FH( phase3) promising report of reducing LDL-C by 58.2%. Functional gene addition therapy for FH in clinical trials is in early phase development targeting on LDL receptor.

Nalini Kumari is an accomplished medical professional with over 15 years of experience in Healthcare sector as clinical pharmacologist, Research, pharmacovigilance, regulatory affairs, and medical affairs. Holds an MD in Pharmacology from GMC Nagpur, India, Fellowship in Diabetes Mellitus and has strengthened her leadership and management skills through the Executive Programme in Healthcare Management at IIM Lucknow. She is currently serveing as Assistant Professor in Pharmacology Department at Apollo Institute of Medical Sciences & Research, Hyderabad, where she teaches core pharmacology, guides research, and mentors undergraduate and postgraduate learners. Her career includes significant roles as Principal Investigator at leading CROs such as ZenRise, ClinSync, and Sipra Labs, contributing to over 400 clinical studies involving BA/BE research, pharmacokinetics, and multicentric trials. She is skilled in medical and scientific writing, protocol development, safety reporting, and regulatory documentation. With expertise across multiple therapeutic areas—including diabetology, cardiology, oncology, CNS disorders, and infectious diseases—she has authored numerous publications and presented at national and international conferences. A committed educator, researcher, and clinician, Dr. Nalini brings strong leadership, analytical ability, and a passion for advancing evidence-based medicine, patient safety, and innovation in clinical research.